Cormack Suzanne, Mohammed Ashfaq, Panahi Pedram, Das Rajiv, Steel Alison J, Chadwick Thomas, Bryant Andrew, Egred Mohaned, Stellos Konstantinos, Spyridopoulos Ioakim
Freeman Hospital, Newcastle upon Tyne, UK.
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, UK.
Br J Clin Pharmacol. 2020 Jul;86(7):1387-1397. doi: 10.1111/bcp.14252. Epub 2020 Mar 11.
Following a favourable pilot trial using a single bolus of ciclosporin, it has been unclear why 2 large studies (CYCLE and CIRCUS) failed to prevent reperfusion injury and reduce infarct size in STEMI (ST elevation myocardial infarction). The purpose of this study was to assess the effect of ciclosporin on myocardial injury, left ventricular remodelling and lymphocyte kinetics in patients with acute STEMI undergoing primary percutaneous coronary intervention.
In this double-blind, single centre trial, we randomly assigned 52 acute STEMI patients with an onset of pain of <6 hours and blocked culprit artery to a single bolus of ciclosporin (n = 26) or placebo (n = 26, control group) prior to reperfusion by stent percutaneous coronary intervention. The primary endpoint was infarct size at 12 weeks.
Mean infarct size at 12 weeks was identical in both groups (9.1% [standard deviation= 7.0] vs 9.1% [standard deviation = 7.0], P = .99; 95% confidence interval for difference: -4.0 to 4.1). CD3 T-lymphocytes dropped to similar levels at 90 minutes (867 vs 852 cells/μL, control vs ciclosporin) and increased to 1454 vs 1650 cells/μL at 24 hours.
In our pilot trial, a single ciclosporin bolus did not affect infarct size or left ventricular remodelling, matching the results from CYCLE and CIRCUS. Our study suggests that ciclosporin does either not reach ischaemic cardiomyocytes, or requires earlier application during first medical contact. Finally, 1 bolus of ciclosporin is not sufficient to inhibit CD4 T-lymphocyte proliferation during remodelling. We therefore believe that further studies are warranted. (Evaluating the effectiveness of intravenous Ciclosporin on reducing reperfusion injury in pAtients undergoing PRImary percutaneous coronary intervention [CAPRI]; NCT02390674).
在使用单次大剂量环孢素进行的一次有利的预试验之后，尚不清楚为何两项大型研究（CYCLE和CIRCUS）未能预防ST段抬高型心肌梗死（STEMI）的再灌注损伤并减小梗死面积。本研究的目的是评估环孢素对接受直接经皮冠状动脉介入治疗的急性STEMI患者心肌损伤、左心室重构和淋巴细胞动力学的影响。
在这项双盲单中心试验中，我们将52例疼痛发作时间<6小时且罪犯血管闭塞的急性STEMI患者，在通过支架经皮冠状动脉介入治疗进行再灌注之前，随机分配接受单次大剂量环孢素（n = 26）或安慰剂（n = 26，对照组）。主要终点是12周时的梗死面积。
两组12周时的平均梗死面积相同（9.1%[标准差 = 7.0]对9.1%[标准差 = 7.0]，P = 0.99；差异的95%置信区间：-4.0至4.1）。CD3 T淋巴细胞在90分钟时降至相似水平（867对852个细胞/μL，对照组对环孢素组），并在24小时时增至1454对1650个细胞/μL。
在我们的预试验中，单次大剂量环孢素不影响梗死面积或左心室重构，这与CYCLE和CIRCUS的结果一致。我们的研究表明，环孢素要么未到达缺血心肌细胞，要么需要在首次医疗接触时更早应用。最后，单次大剂量环孢素不足以在重构过程中抑制CD4 T淋巴细胞增殖。因此，我们认为有必要进行进一步研究。（评估静脉注射环孢素对接受直接经皮冠状动脉介入治疗的患者减少再灌注损伤的有效性[CAPRI]；NCT02390674）
